Related Experiment Videos

Lynch syndrome genes

Päivi Peltomäki1

  • 1Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, P.O. Box 63, Haartmaninkatu 8, 00014, Finland. Paivi.Peltomaki@Helsinki.Fi

Familial Cancer
|September 2, 2005
PubMed

Insights

Mutations in DNA mismatch repair (MMR) genes like MLH1 and MSH2 are linked to Lynch syndrome. Further research is needed to understand the molecular basis of genetic changes and their clinical features.

Area of Science:

  • Genetics
  • Oncology
  • Molecular Biology

Background:

  • DNA mismatch repair (MMR) gene mutations discovered between 1993-1995.
  • Four MMR genes (MSH2, MLH1, MSH6, PMS2) are linked to hereditary nonpolyposis colorectal cancer (HNPCC)/Lynch syndrome.
  • PMS2 mutations are associated with Turcot syndrome; MLH3 and PMS1 roles are less clear.

Purpose of the Study:

  • To review known mutations in MMR genes associated with HNPCC/Lynch syndrome.
  • To explore the functions of MMR gene products beyond DNA repair.
  • To investigate the molecular basis of genotype-phenotype correlations in HNPCC/Lynch syndrome.

Main Methods:

  • Database review of MMR gene mutations.
  • Analysis of known functions of MMR gene products.
  • Literature review on genotype-phenotype correlations.

Main Results:

  • Approximately 500 HNPCC-associated MMR gene mutations are known.
  • MLH1 (50%), MSH2 (40%), and MSH6 (10%) are the most frequently mutated genes.
  • MMR genes have functions beyond DNA repair, and diverse pathogenicity mechanisms exist.

Conclusions:

  • Significant advances have been made in understanding MMR gene mutations in HNPCC/Lynch syndrome.
  • Further research is required to elucidate the molecular mechanisms linking genetic alterations to clinical manifestations.

Related Concept Videos

Pleiotropy01:33

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
Lethal Alleles02:41

Lethal Alleles

Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Sex-linked Disorders01:43

Sex-linked Disorders

Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
X-linked Traits01:19

X-linked Traits

In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.
X-linked Traits01:19

X-linked Traits

In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.
Sex Linked Disorders01:43

Sex Linked Disorders

Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.